Gabriel Fontaine

Major bleeding with dabigatran and rivaroxaban in patients with atrial fibrillation: a real-world setting.

Background: Although the rate of bleeding among patients with atrial fibrillation (AF) taking novel oral anticoagulants in randomized controlled trials is described, the rate of bleeding with “real-world” use is uncertain. Methods: We conducted a retrospective electronic medical record interrogation and subsequent chart review among patients within Intermountain Healthcare between October 2010 and November 2012. Patients were included if they had a diagnosis of AF and were receiving either dabigatran or rivaroxaban. Rates of major bleeding were calculated. Results: Among 2579 patients, 13 (0.5%) experienced major bleeding (95% confidence interval [CI] 0.23-0.77), 5 (0.19%) experienced intracranial hemorrhage (95% CI 0.02-0.36), and 2 (0.08%) experienced fatal bleeding. Of the 13 patients experiencing a major bleed, 8 (61.5%) would have been excluded from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) clinical trials. Conclusion: We observed a rate of major bleeding similar to that reported in randomized clinical trials among patients with AF prescribed dabigatran or rivaroxaban.

Valproate for agitation in critically ill patients: A retrospective study

Purpose: The purpose was to describe the use of valproate therapy for agitation in critically ill patients, examine its safety, and describe its relationship with agitation and delirium. Materials and methods: This retrospective cohort study evaluated critically ill adults treated with valproate for agitation from December 2012 through February 2015. Information on valproate prescribing practices and safety was collected. Incidence of agitation, delirium, and concomitant psychoactive medication use was compared between valproate day 1 and valproate day 3. Concomitant psychoactive medication use was analyzed using mixed models. Results: Fifty‐three patients were evaluated. The median day of valproate therapy initiation was ICU day 7, and it was continued for a median of 7 days. The median maintenance dose was 1500 mg/d (23 mg/kg/d). The incidence of agitation (96% vs 61%, P < .0001) and delirium (68% vs 49%, P = .012) significantly decreased by valproate day 3. Treatment with opioids (77% vs 65%, P = .02) and dexmedetomidine (47% vs 24%, P = .004) also decreased. In mixed models analyses, valproate therapy was associated with reduced fentanyl equivalents (−185 &mgr;g/d, P = .0003) and lorazepam equivalents (−2.1 mg/d, P = .0004). Hyperammonemia (19%) and thrombocytopenia (13%) were the most commonly observed adverse effects. Conclusions: Valproate therapy was associated with a reduction in agitation, delirium, and concomitant psychoactive medication use within 48 hours of initiation.

Venous Thromboembolism in Critically Ill Medical Patients Receiving Chemoprophylaxis: A Focus on Obesity and Other Risk Factors.

Purpose: To compare the incidence of 90-day venous thromboembolism (VTE) in obese critically ill medical patients receiving VTE chemoprophylaxis with nonobese patients of similar illness severity. We also identified other VTE risk factors. Methods: Eligible patients spent ≥24 hours in an intensive care unit between November 2007 and November 2013 and received VTE chemoprophylaxis within 48 hours of admission. The primary outcome was 90-day VTE. Results: A total of 11 111 patients were evaluated, of which 1732 obese and 1831 nonobese patients were enrolled with mean BMIs of 38.9 ± 9.2 kg/m2 and 24.5 ± 3.1 kg/m2 and mean Acute Physiology and Chronic Health Evaluation II scores of 28.4 ± 11.8 and 26.6 ± 11.7, respectively. The rate of 90-day VTE for the total cohort, obese, and nonobese patients was 6.5%, 7.5%, and 5.5%, respectively. Obese patients were more likely to develop VTE compared with nonobese patients (odds ratio [OR]: 1.41; 95% confidence interval [CI]: 1.03 -1.93). Other risk factors significantly associated with 90-day VTE included prior VTE (OR: 3.93; 95% CI: 1.83-8.48), trauma with surgery in the previous 30 days (OR: 3.70; 95% CI: 1.39-9.86), central venous catheters (OR: 2.64; 95% CI: 1.87-3.72), surgery within 90 days (OR: 2.40; 95% CI: 1.61-3.58), mechanical ventilation (OR: 1.94; 95% CI: 1.39-2.71), male sex (OR: 1.55; 95% CI: 1.13-2.14), and increasing age using 1-year increments (OR: 1.02; 95% CI: 1.01 -1.03). Conclusions: The rate of VTE in critically ill medical patients remains high despite standard chemoprophylaxis. Obesity is among 8 risk factors independently associated with 90-day VTE.

Repurposing valproate, enteral clonidine, and phenobarbital for comfort in adult ICU patients: a literature review with practical considerations

Provision of adequate sedation is a fundamental part of caring for critically ill patients. Propofol, dexmedetomidine, and benzodiazepines are the most commonly administered sedative medications for adult patients in the intensive care unit (ICU). These agents are limited by adverse effects, need for a monitored environment for safe administration, and lack of universal effectiveness. Increased interest has recently been expressed about repurposing older pharmacologic agents for patient comfort in the ICU. Valproate, enteral clonidine, and phenobarbital are three agents with increasing evidence supporting their use. Potential benefits associated with their utilization are cost minimization and safe administration after transition out of the ICU. This literature review describes the historical context, pharmacologic characteristics, supportive data, and practical considerations associated with the administration of these agents for comfort in critically ill adult patients.

Comparative thrombosis risk of vascular access devices among critically ill medical patients

BACKGROUND Central venous catheters (CVC) and peripherally inserted central catheters (PICCs) are central vascular access devices (CVADs) that facilitate administration of medications among critically ill patients. Both are associated with risk of venous thromboembolism (VTE). The relative risk of VTE between these catheter types is not well defined. We report the rate of VTE in intensive care unit (ICU) medical patients receiving PICC, CVC, both, or neither. METHODS We conducted a single-center, retrospective cohort study of medical-ICU patients between November 2007 and November 2013 grouped by receipt of CVC, PICC, both, or neither. The primary outcome was the rate of 30-day symptomatic venous thrombosis (upper and lower deep vein thrombosis and pulmonary embolism). Cox modeling was used to analyze this population and adjust for comorbidities which could contribute to VTE. Secondary outcomes included VTE location, major bleeding, and all-cause mortality among patients with and without CVADs. RESULTS We analyzed 5788 patients. CVADs were placed in 2403 (42%) patients (PICC, n = 816; CVC, n = 1153; both, n = 434). Compared with no CVAD, the hazard ratio (HR) for 30-day VTE was 1.81 (95% CI 1.52-2.17) for any CVAD, 1.90 (95% CI 1.52-2.37) for PICC, 1.57 (95% CI 1.26-1.96) for CVC, and 2.70 (95% CI 2.09-3.47) for both. PICCs had a non-significantly higher HR for VTE compared with CVC (1.21; 95% CI 0.94-1.55). For patients with both a CVC and PICC the HR for VTE was 1.72 times that of solitary CVAD (95% CI 1.32-2.23). CONCLUSIONS Among critically ill medical patients, PICCs and CVCs were associated with increased risk of VTE. Placement of both conferred higher risk of VTE compared with either alone.

649: INFLUENZA VIRAL INFECTION AND VENOUS THROMBOEMBOLISM IN CRITICALLY ILL PATIENTS

Critical Care Medicine • Volume 46 • Number 1 (Supplement) www.ccmjournal.org Learning Objectives: Anecdotal reports suggest risk of venous thromboembolism (VTE) is higher among critically ill patients with influenza, especially those with the 2009 H1N1 Influenza A virus, compared with those who have other respiratory viruses. This has yet to be confirmed. Methods: We conducted a multicenter, retrospective cohort study, including critically ill patients with a positive respiratory virus test spending ≥ 24 hours in an ICU between November 2007 and August 2016. The primary analysis compared in-hospital VTE rates between patients with and without influenza, while the secondary analysis compared the same between patients with and without confirmed 2009 H1N1 Influenza A. Patients were excluded if they received therapeutic anticoagulation within 48 hours of admission, had surgery or trauma within 7 days prior to or following admission, diagnosed thrombophilia, or both influenza and other respiratory viruses. Interquartile intervals (IQI) were reported along with medians. Odds ratio (OR) 95% confidence intervals (CI) were computed using a Wald normal approximation, along with Chi-square test pvalues. The false discovery rate (FDR) of the secondary analysis was limited at ≤ 5% per the Benjamini-Hochberg method. Results: Of the 1300 patients with respiratory viruses, 387 (30%) had influenza, 123 of which were H1N1. Median age was 58 years (44–69), median APACHE II score was 19 (14–26), and 64% (n = 832) of patients were mechanically ventilated. In-hospital VTE occurred in 7.5% of patients with influenza and in 8.4% with other respiratory viruses (OR 0.88, 95% CI 0.56 1.4, P = 0.571), and in 12% and 7.7% in respiratory viral patients with and without H1N1, respectively (OR 1.7, 95% CI 0.93 to 3.0, FDR-adjusted P = 0.170). Conclusions: VTE incidence was not significantly different between critically ill respiratory viral patients with and without influenza. Although the estimated in-hospital VTE incidence was higher among critically ill respiratory viral patients with H1N1, the difference was not statistically significant.

Alteplase for acute ischemic stroke after heparin reversal with protamine – a case report and review

Few patients presenting with acute ischemic stroke (AIS) are eligible for alteplase, especially those receiving ongoing anticoagulation. We describe the first reported case of a patient receiving full‐dose intravenous (IV) alteplase for AIS after heparin reversal with protamine. A 73‐year‐old man presented with AIS. He was treated with IV heparin, tirofiban, loading‐dose prasugrel, and aspirin before percutaneous coronary intervention (PCI) for placement of a right coronary artery stent. One hour following PCI, he abruptly developed left hemiparesis and dysphagia. The National Institutes of Health Stroke Scale was 12, and activated partial thromboplastin time (aPTT) was longer than 150 seconds. Head computed tomography (CT) showed no acute pathology, and CT angiogram showed no large‐vessel occlusion amenable to mechanical thrombectomy. Repeat aPTT, obtained 45 minutes later, was 110 seconds, at which time protamine 40 mg IV was administered. At 144 minutes from last known well time, full‐dose IV alteplase (0.9 mg/kg) was administered. Follow‐up head imaging at 25 hours showed right pontine and cerebellar AIS with no evidence of hemorrhage. The patient was discharged to inpatient rehabilitation 2 days later. Modified Rankin Scale at 3 months was 3, improved from 5 at discharge. Given the lack of adverse events associated with IV alteplase in our patient, we advocate cautious evaluation for potential reversal of acutely administered anticoagulation to facilitate alteplase administration in severely disabled patients who are not eligible for mechanical intervention and would have been excluded from definitive AIS treatment.

1962: LOSS OF LIMB SECONDARY TO PROPOFOL EXTRAVASATION

Crit Care Med 2016 • Volume 44 • Number 12 (Suppl.) positioning for this surgery involved steep Trendelenburg with the arms tucked at the patient’s sides using plastic sleds due to patient’s morbid obesity. Post-op, pt. made 100 cc/hour of urine overnight in the ICU. By POD 2, Cr declined to 1.5, while UOP was 50–300 cc/hour. The upper extremities were noted to be slightly swollen, and patient complained of bilateral upper extremity weakness in thumb and first finger. CPK was 16,808. Serum myoglobin was 1.21 (0–0.09). A bicarbonate infusion was begun, along with aggressive hydration. A duplex of the upper extremities revealed small clot in cephalic vein only. An orthopedic consult felt no operative intervention was indicated. CPK and Cr. continued to improve. On POD 5, CPK dropped to 5169, and Cr was 1.1. Pt. was discharged home on POD 10 with Cr 1.4. Finger tingling was improving. Results: Factors contributing to rhabdomyolysis in this patient include: morbid obesity, arms tightly tucked to sides, duration of surgery, steep Trendelenburg positioning with prolonged immobility, and prolonged insufflation of the abdomen. It is important to appreciate the interaction of these factors in a morbidly obese patient for robotic surgery. Learning Points: As robotic surgery expands its reach and encompasses more extensive operations, the potential for complications also increases. This case describes rhabdomyolysis post robotic radical cystectomy. It illustrates the importance of considering multiple disparate factors (steep Trendelenburg, lengthy surgery, morbid obesity, arms tucked, and prolonged abdominal insufflation) that can interact synergistically to produce rhabdomyolysis.

596: CHEMOPROPHYLAXIS PLUS ASPIRIN AND INCIDENT VENOUS THROMBOEMBOLISM IN CRITICALLY ILL MEDICAL PATIENTS.

Crit Care Med 2016 • Volume 44 • Number 12 (Suppl.) or rVIIa administration. Secondary endpoints included major surgical bleeding events, blood product administration (pRBCs, FFP, platelets, cryoprecipitate), and the need for repeat PCC or rVIIa doses. Results: In all, 70 patients were included, 27 (38.6%) received PCC and 43 (61.4%) received rVIIa. Baseline characteristics were similar between the two groups. The median dose of PCC was 24.6 units/kg. The median dose of rVIIa was 35 mcg/kg. There was no difference in the incidence of thrombotic events between the two groups 3/27 (11.1%) versus 6/43 (14%), respectively (p=0.99). There was also no difference in the incidence of major surgical bleeding events between the two groups 5/27 (18.5%) versus 13/43 (30.2%), respectively (p=0.4). Patients receiving PCC required less repeat perioperative doses compared to those who received rVIIa, 3/27 (11.1%) versus 15/43 (34.9%), respectively (p=0.047). No differences were found in blood product administration between the two groups. Conclusions: There was no difference in the incidence of thrombotic or bleeding events in liver transplant patients who received either PCC or rVIIa. Further research is needed to guide exogenous coagulation factor administration in this patient population.

843: THREE- VS FOUR-FACTOR PROTHROMBIN COMPLEX CONCENTRATE IN WARFARIN-ASSOCIATED INTRACRANIAL HEMORRHAGE

Crit Care Med 2016 • Volume 44 • Number 12 (Suppl.) Data were collected by chart review of patients with septic shock requiring vasopressor infusion during the study period. Results: Baseline characteristics were similar between patients in the pre-intervention (n=74) and post-intervention (n=74) groups with the exception of higher APACHE II scores in the pre-intervention group (23 vs 18, p <0.001). Time to achieve goal mean arterial pressure (MAP) was shorter in the post-intervention group (1.3 vs 2.0 hours; p = 0.03) in univariate analysis but not after adjusting for pre-specified confounders. Incidence of new arrhythmias was similar between the two groups (14.9% vs 10.9%; p = 0.567). In multivariable analysis accounting for severity of illness at baseline, admission after the guideline revision was associated with decreased 28-day mortality (OR 0.34; 95% CI 0.16 – 0.71; p = 0.004). Conclusions: Use of a vasopressor guideline restricting AVP initiation in septic patients to those on at least 50 mcg/min of NE appeared to be safe and did not affect the time to reach goal MAP.